REDUCING PAIN; PREVENTING DEPRESSION PI: Jordan F. Karp MD. Co-Is: Debra K. Weiner MD, G. Kelley Fitzgerald PT, PhD. Center Collaborators: Jennifer Morse PhD, Anne Germain PhD, Sati Mazumdar PhD, Stewart Anderson PhD, Abdus Wahed, PhD. Introduction and Specific Aims: Osteoarthritis (OA) pain and associated disability are risk factors for a major depressive episode (MDE).(247) It is established that treating OA pain and disability reduces the severity of comorbid MDE.(248) It is plausible that reducing pain and disability could actually prevent the incidence of future MDE, although this has not yet been tested. Usina an adaptive treatment desion. our overarchina aim of this indicated prevention trial is to explore if improving pain and disability reduces incident MDE amona seniors with knee OA and subthreshold depressive symptoms. Learning-based interventions such as a pain-focused Cognitive Behavioral Therapy (CBT-P) or a kneespecific physical therapy (Manual Therapy and Supervised Exercise (251;258;259); EXERCISE) are routinely prescribed along with analgesics for both pain-control and improved functioning. We recently completed qualitative work with 10 PCPs and 20 seniors living with OA in which we elicited non-analgesic treatment preferences (Karp et al, unpublished data). The majority of both PCPs and patients preferred EXERCISE and CBT-P as the non-analgesic interventions of choice. This acceptance by both clinicians and consumers, and their reimbursable status by Medicare, support their ecological validity and sustainability in primary care. As both interventions are behaviorally activating, improve self-efficacy, and reduce learned helplessness (261,262), they are rational choices for a prevention study of MDE. While both CBT-P and EXERCISE reduce pain and improve functioning(259;268;269), comparative prevention effectiveness trials have not been undertaken. In addition, CBT-P may offer relatively superior protection from MDE because of the attention to problem solving skills, catastrophizing, planning pleasurable activities, and attending to insomnia. Indeed, addressing insomnia may enhance analgesia and promote the prevention of MDE. (270) The order effect of these interventions on reducing pain and disability and preventing depression is also not known; because of attention to psychological health, motivation, and problem solving, individuals first exposed to CBT-P might make better use of EXERCISE than those exposed to EXERCISE and then CBT-P. This project will use an adaptive treatment design(267,271,272) to explore the effect of order. It also links with the Research Design and Biostatistics Unit of the Research Methodology Core for the study of response-adaptive allocation research, and will provide data for the PRC Thompson project. The use of adaptive treatment design will allow our exploration of positive synergies and prescriptive effects inherent in ordered interventions. This is a two stage project. Throughout the study, a collaborative care approach(273;274) with PCPs will be used to offer analgesics to participants. Stage 1 will compare the relative effectiveness of CBT-P and EXERCISE. Stage 2 is adapting interventions based on response to Stage 1. All participants will be followed for 12 months for incident MDE. This project will provide feasibility data about implementing an adaptive treatment design in primary care and following these participants for 12 months post-intervention, will permit our estimation of relative effectiveness of CBT-P and EXERCISE, and is linked with PRC project Thompson (Dynamic Individualized Prediction of Depression Onset). We will also follow subjects receiving enhanced usual care to obtain a benchmark estimate of incident MDE.